As used herein, the term “stem cells” refers to undifferentiated cells that can differentiate into various types of cells constituting tissues of an organism and that can be obtained from respective tissues of an embryo, a fetus and an adult body. Stem cells differentiate into specific cells by a differentiation stimulus (environment) and are capable of proliferation (expansion) by producing identical cells through cell division (self-renewal), unlike differentiated cells whose cell division is arrested. Also, stem cells can differentiate into different cells under different environments or differentiation stimuli, and thus have plasticity in differentiation.
Stem cells are largely divided into two categories: embryonic stem cells (ES cells) which are obtainable from an embryo, can differentiate into all cell types and are totipotent and pluripotent; and multipotent adult stem cells obtainable from each tissue. Embryonic stem cells are undifferentiated cells capable of indefinite proliferation, can differentiate into all cell types, and can be inherited to the next generation through the preparation of germ cells, unlike adult stem cells. Despite such advantages, embryonic stem cells are difficult to use as cell therapeutic agents, due to carcinogenesis, immune rejection, and ethical and legal restrictions.
In recent years, mesenchymal stem cells have been proposed as an alternative to overcome such problems. Mesenchymal stem cells are multipotent cells capable of differentiating into adipocytes, osteocytes, chondrocytes, myocytes, neurocytes and cardiomyocytes and were reported to have the function of regulating immune responses.
The minimal number of cells required in cell therapy or regenerative medicine is about 1×109, which further increases when considering the cells required in a process of establishing culture conditions and standards. In the case of conventional mesenchymal stem cells derived from various origins, at least 10 passages of in vitro experiment are required to obtain such an amount of cells. In such a case, the cells would become aged and modified, which would make them inadequate for use in therapy. This is one of the problems to be solved in current systems for culture of mesenchymal stem cells. In order to use mesenchymal stem cells as cell therapeutic agents, a novel mass production method capable of solving this problem is required.
Mesenchymal stem cells are adhesion-dependent cells and aggregate in a suspension culture process. The in vivo activity of the cells can be increased by such aggregation, but when mesenchymal stem cells are applied to suspension culture for mass production or applied to in vivo culture in the form of single cells, it is required to prevent apoptosis. Suspension culture of single cells is most suitable for highly efficient production of large amounts of mesenchymal stem cells, and thus there need to develop a method for efficient culture of large amounts of mesenchymal stem cells is by developing a method that prevents the death of cells, which do not aggregate, and maintains the activity of cultured cells.
Throughout the specification, a number of publications and patent documents are referred to and cited. The disclosure of the cited publications and patent documents is incorporated herein by reference in its entirety to more clearly describe the state of the related art and the present disclosure.